Exploring porcine gastric and intestinal fluids using microscopic and solubility estimates: Impact of placebo self-emulsifying drug delivery system administration to inform bio-predictive in vitro tools

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dc.contributor.authorBennett-Lenane, Harriet
dc.contributor.authorJørgensen, Jacob R.
dc.contributor.authorKoehl, Niklas J.
dc.contributor.authorHenze, Laura J.
dc.contributor.authorO'Shea, Joseph P.
dc.contributor.authorMüllertz, Anette
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderKøbenhavns Universiteten
dc.contributor.funderIrish Research Councilen
dc.contributor.funderHorizon 2020en
dc.date.accessioned2021-04-20T10:58:31Z
dc.date.available2021-04-20T10:58:31Z
dc.date.issued2021-02-26
dc.date.updated2021-04-20T10:48:41Z
dc.description.abstractValidation and characterisation of in vitro and pre-clinical animal models to support bio-enabling formulation development is of paramount importance. In this work, post-mortem gastric and small intestinal fluids were collected in the fasted, fed state and at five sample-points post administration of a placebo Self-Emulsifying Drug Delivery System (SEDDS) in the fasted state to pigs. Cryo-TEM and Negative Stain-TEM were used for ultrastructure characterisation. Ex vivo solubility of fenofibrate was determined in the fasted-state, fed-state and post-SEDDS administration. Highest observed ex vivo drug solubility in intestinal fluids after SEDDS administration was used for optimising the biorelevant in vitro conditions to determine maximum solubility. Under microscopic evaluation, fasted, fed and SEDDS fluids resulted in different colloidal structures. Drug solubility appeared highest 1 hour post SEDDS administration, corresponding with presence of SEDDS lipid droplets. A 1:200 dispersion of SEDDS in biorelevant media matched the highest observed ex vivo solubility upon SEDDS administration. Overall, impacts of this study include increasing evidence for the pig preclinical model to mimic drug solubility in humans, observations that SEDDS administration may poorly mimic colloidal structures observed under fed state, while microscopic and solubility porcine assessments provided a framework for increasingly bio-predictive in vitro tools.en
dc.description.sponsorshipKøbenhavns Universitet, University of Copenhagen (Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences); Irish Research Council (Post Graduate Scholarship Project number GOIPG/2018/883); European Commission ((PEARRL European Training network, which has received funding from the Horizon 2020 Marie Sklodowska-Curie Innovative Training Networks programme under grant agreement No. 674909); (UNGAP COST ACTION CA16205 funded by the Horizon 2020 Framework Programme of the European Union))en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid105778en
dc.identifier.citationBennett-Lenane, H., Jørgensen, J. R., Koehl, N. J., Henze, L. J., O'Shea, J. P., Müllertz, A. and Griffin, B. T. (2021) 'Exploring porcine gastric and intestinal fluids using microscopic and solubility estimates: Impact of placebo self-emulsifying drug delivery system administration to inform bio-predictive in vitro tools', European Journal of Pharmaceutical Sciences, 161, 105778 (11 pp). doi: 10.1016/j.ejps.2021.105778en
dc.identifier.doi10.1016/j.ejps.2021.105778en
dc.identifier.endpage11en
dc.identifier.issn0928-0987
dc.identifier.journaltitleEuropean Journal of Pharmaceutical Sciencesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/11211
dc.identifier.volume161en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/674909/EU/Pharmaceutical Education And Research with Regulatory Links: Innovative drug development strategies and regulatory tools tailored to facilitate earlier access to medicines/PEARRLen
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0928098721000804
dc.rights© 2021 The Authors. Published by Elsevier B. V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBio-enabling formulationsen
dc.subjectIn vitro toolsen
dc.subjectLandrace pigsen
dc.subjectOral drug deliveryen
dc.titleExploring porcine gastric and intestinal fluids using microscopic and solubility estimates: Impact of placebo self-emulsifying drug delivery system administration to inform bio-predictive in vitro toolsen
dc.typeArticle (peer-reviewed)en
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